Work carried out in the last year has identified selective contributions of the amygdala, PFo and PFm to emotion and reward processing. [unreadable] [unreadable] A wealth of evidence implicates the PFo in reward guided behavior and affect. Lesion and neurophysiology studies have shown that this part of the prefrontal cortex plays a role in representing reinforcement expectations, preferences and rules as well as in marshalling appropriate emotional responses. PFo is comprised of several areas that are cytoarchitectonically distinct, including Walkers areas 11, 13 and 14. Furthermore, on the basis of neuroanatomical connection studies it has been suggested that there may be two distinct regions within the PFo: one region broadly encompasses Walkers areas 11 and 13 and is heavily interconnected with sensory related cortical areas whereas the other includes Walkers area 14 and is more densely interconnected with medial frontal cortex and autonomic structures. Based on these differences we postulated that these two areas make dissociable contributions to reward guided behavior and emotion. [unreadable] [unreadable] To test this hypothesis we evaluated the effects of selective, excitotoxic lesions of areas 11/13 and of area 14 on a battery of reward guided tasks, including reinforcer devaluation and object reversal learning. The first task, reinforcer devaluation, requires association of an object with the value of a particular food reward and a shift in choices of objects when the value of food reward changes. The second task, object reversal learning, requires the ability to alter previously learned stimulus-reward associations when the reward contingency changes. For example, subjects first learn to approach object A in a context in which approaching A yields food reward but approaching object B yields no food reward (A+, B-). After a change in reward contingency, subjects must learn to approach B instead of A to obtain food reward (A-, B+). Areas 11/13, but not area 14, was found to be essential for shifting object choices based on food value. That is, subjects with lesions restricted to areas 11/13 were less able to alter object choices following specific satiety intended to devalue a given food. There was no effect of selective lesions of either areas 11/13 or area 14 on tests of object reversal learning. This is a surprising result because aspirative lesions of PFo, which includes areas 11, 13 and 14 severely disrupt object reversal learning. Future studies need to address whether combined excitotoxic lesions of area 11, 13 and 14 will reproduce the effects on object reversal learning of the aspirative lesion. If so, this would suggest that some functions of PFo are shared among multiple areas. If not, then inadvertant damage to fibers passing through PFo en route to other areas should be considered as a possible explanation for the difference in outcome of the two types of lesions. [unreadable] [unreadable] As for PFm, converging lines of evidence suggest that a portion of PFm known as the anterior cingulate cortex (ACC) represents the expected reward value of a particular action. In addition, several findings suggest a selective role for the ACC in action-reward associations. For example, neurons in the ACC encode actions but not stimuli associated with reward. Also, lesions of the ACC do not impair performance on object reversal learning. Although the ACC appears to be essential for action-reward associations, its role in guiding choices on the basis of changes in reward value remains unclear. [unreadable] [unreadable] We therefore investigated the effects of bilateral ACC lesions in both stimulus-reward associations (using a reinforcer devaluation task) and action-reward associations. There was no effect of ACC lesions on reinforcer devaluation: all subjects adjusted their object choices appropriately following a change in the value of the associated food. We also evaluated stimulus- and action-reward associations using two different reversal learning tasks, one object- and one action-based. The object task involved two objects whereas the action task was carried out using a joystick with two possible movements. In each task subjects had to reverse a previously learned object- or action-reward association. Consistent with earlier reports, ACC lesions had no effect on object reversal learning. By contrast, ACC lesions mildly disrupted the ability to make a new action in line with the reversed action-reward contingency. These findings support the idea that the ACC contributes to action-reward but not object-reward associations.[unreadable] [unreadable] The neurotransmitter serotonin plays a central role in emotion, as evidenced by brain serotonergic abnormalities in emotional disorders and the therapeutic efficacy of drugs targeting this system. At the same time, serotonergic manipulations appear to affect cognitive functions mediated specifically by the PFo. For example, subjects with 5-HT depletion within the prefrontal cortex exhibit impaired performance on reversal learning. Our research makes use of the naturally-occurring differences in the structure of the gene encoding the serotonin transporter (5-HTT), which regulates serotonergic turnover via extracellular clearance. In vitro functional analyses of the 5-HTT gene-linked polymorphic regions (5-HTTLPR) demonstrate lowered transcriptional activity associated with short (S) compared to long (L) alleles. The relationship of 5-HTT genotype to cognitive processing, and the way in which it modulates frontal cortex function is a goal for future research.